Rifaximin diminishes neutropenia following potentially lethal whole-body radiation.

Terrorist attacks involving radiological or nuclear weapons are a substantial geopolitical concern, given that large populations could be exposed to potentially lethal doses of radiation. Because of this, evaluating potential countermeasures against radiation-induced mortality is critical. Gut microflora are the most common source of systemic infection following exposure to lethal doses of whole-body radiation, suggesting that prophylactic antibiotic therapy may reduce mortality after radiation exposure. The chemical stability, easy administration and favorable tolerability profile of the non-systemic antibiotic, rifaximin, make it an ideal potential candidate for use as a countermeasure. This study evaluated the use of rifaximin as a countermeasure against low-to-intermediate-dose whole-body radiation in rodents. Female Wistar rats (8 weeks old) were irradiated with 550 cGy to the whole body and were evaluated for 30 d. Animals received methylcellulose, neomycin (179 mg/kg/d) or variably dosed rifaximin (150-2000 mg/kg/d) one hour after irradiation and daily throughout the study period. Clinical assessments (e.g. body weight) were made daily. On postirradiation day 30, blood samples were collected and a complete blood cell count was performed. Animals receiving high doses of rifaximin (i.e. 1000 or 2000 mg/kg/d) had a greater increase in weight from the day of irradiation to postirradiation day 30 compared with animals that received placebo or neomycin. For animals with an increase in average body weight from irradiation day within 80-110% of the group average, methylcellulose rendered an absolute neutrophil count (ANC) of 211, neomycin rendered an ANC of 334, rifaximin 300 mg/kg/d rendered an ANC of 582 and rifaximin 1000 mg/kg/d rendered an ANC of 854 (P = 0.05 for group comparison). Exposure to rifaximin after near-lethal whole-body radiation resulted in diminished levels of neutropenia.

Exercise-induced lymphocyte apoptosis attributable to cycle ergometer exercise in endurance-trained individuals.

Exercise as a stimulus to induce lymphocyte apoptosis remains controversial. Differences may be due to participant fitness level or the methodology of assessing cell death. Another important issue is the mode of exercise used to induce physiological changes. Treadmill exercise typically induces significant apoptosis in human lymphocytes; however, the effect of cycle exercise is less clear. The 2 main purposes of this study were to assess if cycle ergometer exercise induces similar changes in apoptosis, and to further characterize the morphological method of assessing cell death. Endurance athletes (n = 10; peak oxygen consumption = 55.1 mL.kg-1.min-1) completed a 60-min ride on a cycle ergometer at approximately 80% peak oxygen consumption. Blood samples taken before (PRE) and after (POST) exercise were used to make blood films for apoptotic analysis via the morphological technique. A significant increase was observed in the apoptotic index following cycle exercise (PRE = 7.3 +/- 2%, POST = 12.9 +/- 2%; p < 0.01). On average, it took 42 +/- 9 min to read PRE sample slides, which was significantly longer than the 27 +/- 4 min needed for POST slides (p < 0.01). To our knowledge, this study is the first to report that exercise on the cycle ergometer produces changes in lymphocyte apoptosis. The values measured during this study were about 20% lower than those we have observed following treadmill running, which may be explained by differences in active muscle mass and the resultant physiological stress between the 2 exercise modes. It is likely that cycling may result in reduced immunosuppression, compared with running at the same intensity.